In vivo induction of specific cytotoxic T lymphocytes in mice and rhesus macaques immunized with DNA vector encoding an HIV epitope fused with hepatitis B surface antigen.
DNA immunization offers a novel means to induce humoral and cellular immunity in inbred or in outbred animals. Here we have tested the efficiency of genetic immunization with hepatitis B virus (HBV) envelope-based vectors. In naive primates, injection of a plasmid DNA encoding HBV envelope proteins induced an HBV-specific cytotoxic response and appearance of potentially protective anti-HBs antibodies. Moreover, intramuscular and intradermal injections of a DNA expression vector encoding an epitope of the human immunodeficiency virus envelope fused to the surface protein of the hepatitis B virus (HBsAg) induced strong humoral and cytotoxic responses to antigenic determinants of both viruses in mice and nonhuman primates alike. In addition, in protein-primed Rhesus monkeys B-cell memory was successfully boosted by DNA injection of hybrid vectors and animals subsequently developed a multispecific cellular response. This suggests that DNA-based immunization could be used to boost efficiently and broaden the immune response in individuals immunized with conventional vaccines, regardless of their genetic variability. These results also indicate that it might be possible to rationally design HBsAg-based expression vectors to induce multispecific immune responses for vaccination against hepatitis B and other pathogens.
Le Borgne
S
S
Unité de Virologie et Immunologie Cellulaire, URA CNRS 1157, Paris, France.
Mancini
M
M
Le Grand
R
R
Schleef
M
M
Dormont
D
D
Tiollais
P
P
Rivière
Y
Y
Michel
M L
ML
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006678:HIV / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D007114:Immunization / Q000379:methods; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA